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Understanding USP <665> – A Guide to Single-Use Systems in Pharmaceuticals

Introduction
In the fast-evolving world of pharmaceutical and biopharmaceutical manufacturing, single-use systems (SUS) have brought flexibility, efficiency, and cost savings. However, with their increasing adoption, ensuring product safety and quality has become more critical. The United States Pharmacopeia (USP) <665>, set to become mandatory in May 2026, provides essential guidelines for managing extractables and leachables (E&L) risks. This blog simplifies USP <665>, explaining what it means for manufacturers and how to prepare for compliance.

What Is USP <665>?
USP <665> focuses on the potential risks posed by E&L in SUS. E&L refers to substances that may migrate from plastic components into pharmaceutical products during manufacturing. These substances, called process equipment-related leachables (PERLs), can compromise a drug’s safety, efficacy, and stability.

Examples of components covered by USP <665> include:

  • Tubing, connectors, and filters
  • Bags, bioreactors, and storage containers
  • O-rings, gaskets, and pump surfaces

The chapter outlines a standardized protocol for testing these materials. Depending on the risk level, it involves testing with one or more solvents to identify and quantify potential contaminants.

The Importance of Risk Assessment
USP <665> emphasizes a risk-based approach to identify and mitigate potential issues with SUS components. The process includes:

  1. Identifying Components: Catalog all SUS parts in contact with drug substances or products.
  2. Material Characterization: Understand the chemical composition and potential degradation pathways of each material.
  3. Process Mapping: Analyze where and how the drug interacts with SUS, considering factors like temperature and duration.
  4. Risk Evaluation: Assess the impact of E&L on product safety, factoring in the patient population and dosage form.
  5. Risk Control: Implement strategies like selecting lower-risk materials, optimizing processes, or adding purification steps.

How to Prepare for USP <665> Compliance
To meet the May 2026 deadline, manufacturers should take the following steps:

  1. Review Requirements: Understand the specifics of USP <665>.
  2. Inventory SUS: Identify all single-use components in your processes.
  3. Develop a Testing Plan: Create a detailed roadmap for compliance testing.
  4. Select a Testing Partner: Work with an experienced laboratory like Solvias for accurate and reliable results.
  5. Conduct Testing: Follow the plan and industry best practices for evaluating components.
  6. Analyze Results: Address any issues with corrective actions.
  7. Maintain Documentation: Keep thorough records of testing and compliance activities.

The Role of Analytics in USP <665>
Comprehensive testing is at the heart of USP <665> compliance. Analytical methods used include:

  • Gas Chromatography-Mass Spectrometry (GC-MS): Identifies volatile and semi-volatile compounds.
  • Liquid Chromatography-Mass Spectrometry (LC-MS): Detects non-volatile substances.
  • Inductively Coupled Plasma-Mass Spectrometry (ICP-MS): Measures elemental impurities.

These techniques ensure manufacturers can identify potential risks and safeguard product quality.

How Solvias Can Help
Solvias is a trusted partner for manufacturers navigating USP <665>. With over 20 years of experience and state-of-the-art facilities, we provide:

  • Expertise in polymeric and elastomeric material testing
  • Advanced analytical technologies for E&L assessments
  • Tailored solutions for risk management and compliance

Our Centers of Excellence in the US and Switzerland offer comprehensive services to help streamline the compliance process, saving time and resources while ensuring high standards.

Looking Ahead
As the pharmaceutical industry evolves, so do regulatory standards. USP <665> is a step forward in ensuring the safety and quality of products manufactured using SUS. By preparing now, manufacturers can not only meet compliance requirements but also build trust and confidence in their products.

For more information on USPs or to partner with Solvias, click here.